1/ I have a thread about natural immunity to SARS-CoV-2, but I was asked to do a comparison with vaccine induced immunization. Interestingly, deep analysis of the two is largely missing. A recent study will do the job,
science.sciencemag.org/content/early/…
2/ but we need to focus on results, not conclusions, because even though the study was designed to compare the two types of immunization, plus added the effect of a booster jab on top of infection, the interpretation is a bit twisted to mostly compare the 2 jab scenarios.
3/ Quote:
"Three individuals who previously showed a response, despite lack of laboratory evidence for infection (therefore presumably a cross-reactive response to an endemic human coronavirus) showed an unchanged or decreased [T cell] response to spike after vaccination."
4/ Apparently, in some cases, vaccination can decrease T cell response to real antigen exposure, which is needless to say, not good. A preprint described the phenomenon earlier, although only following the second, so-called booster, jab:
5/ Next quote:
"Twenty of 22 vaccinated naïve individuals had detectable S1 specific ASC comprising 0.02% to 1.54% of the memory B cell (MBC) pool. By comparison, all vaccinated post infection individuals had detectable S1 specific ASCs (1.90–50% of MBC pool)."
6/ This boost seems totally unnecessary in the vast majority of people, perhaps with the exception of the lowest end of the spectrum (non-responders). Potential harms of 50 % !!! of all ASCs dedicated to a single subunit of a single virus? Certainly not normal.
7/ On to the next part in the paper: "Vaccinated naïve individuals made a lower nAb response to WT virus than seen following natural infection at 16–18 weeks" Finally, a concrete comparison. It shows that natural infection induced immunity is at least as good as vaccination.
8/ Next quote: "there was a significantly enhanced nAb response in vaccinated post infection individuals compared with the vaccinated naïve group (Fig. 1G), the mean value being 25,273 compared to 420, that is, a 60-fold increase."
Is it a useful bump? Is the higher the better?
9/ Move on to "The data in Fig. 1 indicate that there is a strong prime-boosting effect of prior infection on single dose vaccination. Augmentation is seen more strongly in MBC frequency, anti-RBD, and nAb responses than for T cell response frequency.
10/ …Furthermore, there was no correlation between S1 ASC frequency and T cell response frequency (Fig. 1H). There is, however, a correlation between S1 ASC and RBD antibody titers"
11/ This finding suggests that the body reacts to vaccination after infection as if there was an acute reinfection.
It is not universal "boosting of immunity", just triggering Ab secretion from existing (and memory) cells.
12/ Seems counterproductive, except for Pfizer shareholders and executives?

Next quote: "The majority of SARS-CoV-2 immune naïve individuals made no nAb response to the B.1.1.7 (18/20) and B.1.351 (17/20) variants after single dose vaccination.
13/ …In contrast, almost all vaccinated post infection individuals made a strong nAb response to the B.1.1.7 (24/24) and B.1.351 (23/24) variants after a single dose vaccination with a 46-fold (B.1.1.7) and 63-fold (B.1.351) increase in mean nAb IC50"
14/ I'm confident that this is what happens upon reexposure to the virus, e.g. a variant. too. So what is the point of the booster again? Confirm the effect with virus and forget the excess jab.
15/ I am ready to volunteer, but you'll need an uncommon strain, because most likely I have already been exposed to the B117.

"Worryingly, after single dose vaccination, 90% (18/20) of vaccinated naïve individuals showed no detectable nAbs (IC50 < 50) against B.1.1.7"
16/ Defending the vaccine here, but it's not necessarily worrying. There is clearly no 90 % breakthrough rate of B117 in 3w+ primer vaccinated people. This is the striking problem of the unjustified strong focus on systemic antibodies in a fundamentally respiratory infection.
17/ Let's jump to the part "We initially looked at T cell responses following natural infection and found that at 16–18 weeks post infection, the N501Y mutation appeared to have no substantial differential impact on the T cell response (Fig. 2F), unlike nAb recognition."
18/ The authors also get it. That's why we have T cells, these can help refine Ab responses upon "variant" exposure. Miraculously, it already works in vaccinated people, despite the much narrower antigen range used.
19/ Apparently, the full spike is a long enough polypeptide sequence to provide many antigens for T cell receptors.

Next one, please.
20/ "vaccinated naïve individuals made an anti S1 RBD Ab response with a mean titer of about 100 U/ml at d22 (±2d) after vaccination, roughly equivalent to the mean peak Ab response after natural infection.
21/ …However, the spike T cell response after one dose was lower than after natural infection, and for 30% of vaccinees no response could be measured."
One jab is clearly inferior to natural infection. No response in 30 % sounds too high a proportion?
22/ A long quote is imminent, beware and pay attention please. "It is striking that the high IC50 titers in those vaccinated after infection provide such a large protective margin that responses to authentic B.1.1.7 and B.1.351variants are also high.
23/ …In contrast, nAb responses in individuals several months on from mild infection show much lower IC50s against B.1.1.7 and B.1.351, often <100. Similarly, the majority of responses in naïve individuals after one dose show weak recognition of B.1.1.7 and B.1.351.
24/ This finding indicates potentially poor protection against B.1.1.7 and B.1.351 in individuals who have experienced natural infection or who have only had one vaccine dose."

Firstly, it is not striking, rather expected.
25/ As suggested above, this is likely a normal response to reinfection. At least the body percieves the reappearance of antigens as re-exposure. Secondly, this finding still does not indicate poor protection against the mentioned variants.
26/ Perhaps it takes a day or two more and mild instead of no symptoms, but it's highly unlikely that the vast majority of people would experience variant infection the same way as an immune naïve individual.
27/ Last quote: "second dose vaccination in one dose vaccinated post infection individuals offers no additional enhancement."
A second "booster" for a previously infected person was even shown to suppress cellular immunity, which sounds straight harmful. See quote tweet in 4/.
28/ TL;DR
Natural infection induced immunity is typically at least as robust as the one elicited by double vaccination, but the former protects more effectively against emerging variants. Moreover, level of systemic Ab is not necessarily the best benchmark to use.
/End
Extending evidence base with this preprint. On a side note, time since immunization, whether via infection or vaccine, is an important factor that has to be taken into consideration when comparisons are made.

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More from @gerdosi

28 Apr
There’s a curious correlation between countries/regions of high prior SARS2 exposure and a resurgence upon the start of mass V immunization programs. I’ve been thinking a lot about this lately, and the only explanation that could fit observations is… 1/
bmj.com/content/372/bm…
reactivation of dormant viruses in the population. (Seasonal) respiratory viral dormancy has been debated a lot for decades, but there’s still no consensus on where exactly these virions could lay dormant in the body, nor on the trigger(s) & mechanism(s) responsible for… 2/
reactivation. In light of recent research, my (educated?) guess is that the small intestine, and associated immune structures, is more likely place for this to occur than the respiratory tract. Admittedly, this is speculative, but neither implausible nor could I come up with… 3/
Read 8 tweets
20 Jan
The autoimmunity problem raised by below article requires rethinking of pathophysiology and treatment of severe COVID-19. The level of mimicry between spike and human peptides is very high (see attached figure from a researcher featured in the article).
nature.com/articles/d4158… Image
Unfortunately, this seems more than theoretical matches.
“SARS-CoV-2 antibodies had reactions with 28 out of 55 tissue antigens, representing a diversity of tissue groups that included barrier proteins, gastrointestinal, thyroid and neural tissues” & more.
frontiersin.org/articles/10.33…
An excellent bird’s view of the same topic.
cell.com/cell-systems/f…
Read 7 tweets
28 Dec 20
New mRNA vaccine technologies may offer 94-95 % efficacy. What an achievement of 21st century science!
On the other hand, good old natural immunity provides 100 % protection from symptomatic COVID-19, as shown in the study of 12.5k healthcare workers below.
Another large study finds precisely the same thing: 100 % natural immune protection from symptomatic COVID-19 within 6 months of first infection. journalofinfection.com/article/S0163-…
What could provide lasting protection? Repeated exposure.
Tissue resident memory T cell presence “required airway vaccination and antigen persistence in the lung, as non-respiratory routes of vaccination failed to support long-term lung TRM maintenance.”
nature.com/articles/s4138…
Read 10 tweets
13 Dec 20
What a coincidence
“The binding epitope on S harbors a sequence motif unique to SARS-CoV-2 (not present in other SARS-related coronaviruses), which is highly similar in both sequence and structure to the bacterial superantigen staphylococcal enterotoxin B”
pnas.org/content/117/41… Image
Now, this story keeps unfolding.
“the trimeric spike protein of SARS-CoV-2 could bind to TLR4 directly and robustly activate downstream signaling in monocytes and neutrophils.” Via MyD88 and NFκB
See how MyD88 activation is THE problematic pathway, especially when amplified by elevated LPS exposure. I.e. by metabolic diseases.
How the two pathways join at this signaling node
👇🏻👇🏻👇🏻
journals.sagepub.com/doi/10.1177/17…
Read 21 tweets
27 Oct 20
1/ Thread on immunity in the respiratory system: how it does and doesn't work (i.e. myths), simplified as much as I could. I’ll use the apropos of a new press release by Imperial College. To avoid mainstream media fantasies, let's use the original piece. imperial.ac.uk/news/207333/co…
2/ The main pillars of mucosal immunity in the respiratory system are:
– Innate immunity. This ancient part includes the physical barrier: mucus production and continuous flow upwards, driven by ciliary epithelial cells. There are also phagocytes ("eating cells") and…
3/ …other cellular components that produce signaling molecules, set traps, etc.

– Adaptive immunity
---> B & plasma cells that release antibodies into the airways through the single cell layer called the epithelium.
Read 21 tweets
8 Oct 20
Bacteria-fighting neutrophils in the URT ⬆️ risk of viral infections. Implications are huge, pinpointing a potential unifying mechanism. In metabolic diseases a similar elevation of activated neutrophils occurs. What about periodontitis in severe COVID-19? imperial.ac.uk/news/206253/ba…
From the study:
“those who resisted infection showed a transient boost in mucosal markers of innate immune activation for several days after viral administration and no subsequent viral replication.”
In the meantime everybody is obsessed with antibodies circulating in the arms?
Two major components of mucosal immunity largely ignored in respiratory infections. SIgA is the other one:
“Prior RSV-specific nasal IgA correlated significantly more strongly with protection from [PCR-]confirmed infection than serum neutralizing antibody”
atsjournals.org/doi/10.1164/rc…
Read 4 tweets

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